The primary objective of the proposed study is to characterize the single stranded DNA (SDNA)-anti-SDNA, SDNA-anti-native DNA (NDNA), and NDNA-anti-NDNA immune complex systems in the sera of patients with Systemic Lupus Erythematosus, clarify the relationship of each of these systems to the clinical course of the disease in patients with different clinical manifestations, and determine the source of the DNA. DNA isolated from serum will be studied by buoyant density CsCl gradient ultracentrifugation and by hybridization techniques in order to determine if all or part of the DNA is homologous to mammalian and/or microbial DNA. The site of single stranded DNA release will be sought by immunofluorescence studies of tissue lesions of these patients. In addition, other circulating immune complex systems will be characterized and relationship to disease activity studied, including double stranded RNA-anti-double stranded RNA, ribonucleoprotein-anti-ribonucleoprotein, and gamma globulin-anti-gamma globulin. These studies will be conducted in patients with Systemic Lupus Erythematosus (SLE) and renal disease, SLE with systemic symptoms and no renal disease, and particular attention will be directed to the study of patients with SLE and neurological manifestations. In the latter group of patients, in addition to serological studies, immunofluorescence and elution of central nervous system tissue and choroid plexus will be performed to assess the nature of immune complexes and possibly auto-antibodies deposited in central nervous system tissue. A possible mechanism for the immunogenicity of SDNA will be studied in patients with procainamide induced SLE by studying the specificity of anti-SDNA antibodies and assaying sera for the presence of procainamide denatured SDNA. In order to gain further insight into the role of SDNA immune complex systems in other types of tissue injury, sera from patients with rheumatoid arthritis and chronic active hepatitis will be studied for the presence of SDNA and NDNA antigen during the course of the disease.